Abstract
The eye is a relatively isolated tissue compartment, which provides advantages for utilization of small interfering RNA (siRNA). Feasibility of using siRNA for treatment of choroidal neovascularization has been demonstrated using siRNA directed against vascular endothelial growth factor (VEGF) or VEGF receptor 1 (VEGFR1), and both of these approaches are being tested in clinical trials. The results with VEGFR1 siRNA show that VEGFR1 is pro-angiogenic in the eye and is not a decoy receptor as it is in developmental angiogenesis. Topical delivery of siRNAs directed against VEGF or its receptors has also been shown to suppress corneal neovascularization. Signaling through transforming growth factor-beta receptor 2 (TGFbetaR2) has been implicated in excessive ocular scarring and TGFbetaR2 siRNA has shown benefit in a model relevant to excessive scarring after glaucoma filtration surgery. RNAi has been used to identify genes that promote apoptosis or oxidative damage in retinal cells and could be the basis of new treatments for glaucoma or photoreceptor degenerations. In cultured cells derived from ocular tissues, siRNA has become a valuable tool to explore the potential role of various genes in ocular disease processes. Based upon this early experience in vivo and in vitro, it appears that siRNAs may be valuable to help define the pathogenesis and develop new treatments for several ocular diseases.
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